Apparatus for controlled delivery of liquids

ABSTRACT

An apparatus for a controlled delivery of a liquid preparation from a cylindrical liquid container, which has a liquid outlet at its front end and a movable wall, which acts like a piston at its rear end is provided. The driving force acting on the movable wall for expelling the liquid from the container is generated by means of a piston rod in connection with a piston, which by the action of the atmospheric pressure is urged into a space where a vacuum has been established. The amount delivered can be varied according to different modes by providing an auxiliary force which acts on the piston during the initial stage of its movement into the vacuum space.

TECHNICAL FIELD

The present invention refers to an apparatus for a controlled deliveryof liquids. More specifically, the invention refers to an apparatus forsuch a delivery which may be varied during the time of delivery. Stillmore specifically, the invention refers to an apparatus for such adelivery of a pharmaceutical preparation by parenteral injection orinfusion. Especially, the invention refers to such an apparatus which isindependent of any external power source for its function.

BACKGROUND OF THE INVENTION

Devices for a controlled delivery of liquids, especially by parenteralinjection or infusion, are previously known. Such devices are used whenit is desired to administer a liquid preparation to a patient for anextended period of time. The preparation is expelled from a suitablecontainer by some suitable driving force, and the delivery is controlledby arranging a suitable constriction in the conduit or line from thecontainer to the patient receiving the administered liquid.

There are no problems in arranging this controlled delivery in ahospital where the driving force may simply be the hydrostatic headachieved by hanging up the container in an infusion stand of awell-known type. Furthermore, a number of infusion pumps are known,which are dependent on an external power source, such as electricity orcompressed air. These pumps may also be programmed to give a deliverywhich can be varied with the time.

However, difficulties arise when a controlled infusion or injection isto be administered for an extended time where hospital facilities arenot available, such as in the ambulatory treatment of accidents orsudden illnesses, such as heart attacks. For instance, in the treatmentof a heart infarct, an administration of an antithrombotic agent, suchas streptokinase, will often have to be given for an extended time ofabout an hour or more, where no programmed infusion pumps depending onan external power source are available.

There have been developed devices for administering parenteralinjections or infusions for an extended period of time, which are notdependent on any external power source for driving an infusion pump. Inone suitable embodiment of such devices, a vacuum is established in achamber which is provided with a movable piston. The atmosphericpressure on the opposite side of the piston strives to move the pistoninto the vauum chamber, and through a suitable mechanical connection,such as a piston rod, this movement actuates a piston in an infusionpump or syringe to expel a preparation from said pump or syringe toadminister it to a patient. The time for the administration iscontrolled by a suitable constriction in the flow path of theadministered preparation.

Such devices have a number of important advantages. As the driving forceis achieved by the atmospheric pressure acting against a vacuum, and notby any kind of gas-generating material, as is also previously known theforce is constant over the time for administration. This means that aconstant amount of the preparation is administered per unit of time.Furthermore, no gas-generating and potentially hazardous materials haveto be handled. Also, in a specially preferred embodiment, the vacuum isestablished immediately before an infusion is administered. Thiseliminates the risk that the device becomes inoperative because of leakshaving destroyed the pre-established vacuum.

Devices of the type mentioned above have been described in theinternational patent application No. PCT/SE91/00506, and have given goodservice. However, there is still room for improvement of these devices.As stated above, the amount of preparation administered per unit of timeis essentially constant, because of the constant pressure acting on thepiston against the vacuum. In certain applications, however, it isdesired to administer a greater amount of preparation during an initialstage of the infusion, and a smaller, constant amount per unit of timeduring a later stage. One example of such an application is when agentsare administered which initially are bound to the blood cells and arethus inactivated, and only later will act in their free form. Such isthe case with tissue plasmin activator, TPA, for example. It may also bedesired that said larger amount is constant per unit of time, or that itvaries with time. These objects are achieved through the presentinvention.

SUMMARY OF INVENTION

According to the present invention, a device is provided for acontrolled time-variable delivery of a liquid preparation from acylindrical liquid container, which is provided at its front end with aliquid outlet having a constriction, and at its rear end is providedwith a movable wall which functions like a piston to expel the liquidfrom said container through said outlet, said rear movable wall beingurged forward by mechanical action by a force which is generated by theatmospheric pressure urging a first piston into first essentially emptyvacuum space, and the invention is characterized in that auxiliary meansare arranged to act on said movable wall in the liquid container byexerting a supplementary force on said first piston at an initial stageof its movement into said first vacuum space.

In a first embodiment of the invention, said auxiliary means is apressure spring acting on said first piston against said vacuum space.

In a second embodiment of the invention, said auxiliary means is atleast one auxiliary vacuum space, wherein the atmospheric pressure actson at least one auxiliary piston, which is mechanically coupled to saidfirst piston in said first vacuum space.

In a preferred embodiment of the invention, the device comprises twoessential parts, a delivery unit which contains the preparation to beadministered, and a power unit which contains the vacuum chamber andpiston arrangement that supplies the driving force for the delivery.These two units are arranged to be coupled to each other coaxially, andwhen they are assembled together, the vacuum is established and theatmospheric pressure will start to exert its force on the piston. Thisforce will, by means of a piston rod, be transferred to the piston in aninfusion pump or syringe, to expel the liquid preparation.

In a still further preferred embodiment of the invention, the deliveryunit is arranged as a holder for an injection cartridge of thesingle-chamber or dual-chamber type.

SUMMARY OF THE DRAWINGS

In the drawing,

FIG. 1 is a diagram showing the various modes of delivery in accordancewith the invention.

FIG. 2 shows a delivery unit of a device of the invention.

FIGS. 3 and 4 show an assembled device according to a first embodimentof the invention, and

FIGS. 5 and 6 show a device according to a second embodiment of theinvention. In the description of the devices of the invention, theexpressions "front" and "forward" signify the direction in which theliquid preparation is delivered from said device. Consequently, theexpressions "rear" and "rearward" signify the opposite direction.

DESCRIPTION OF BEST AND VARIOUS MODES FOR CARRYING OUT INVENTION

The diagram in FIG. 1 shows the delivery rate for the liquid preparationas a function of time. Graph A (full line) shows the delivery mode ofthe prior art. In this mode, the delivery rate remains constant from thebeginning and decreases abruptly to zero when the vacuum source isdepleted and the delivery is finished. Graph B (dashed line) shows thedelivery mode according to a first embodiment of the invention. In thismode, the delivery rate is high at the beginning, and then decreasesessentially in a linear manner until it approaches a determined value,where it remains constant until the delivery is finished. Graph C(dot-dashed line) shows the delivery mode according to a secondembodiment of the invention. In this mode, the delivery starts at a highvalue and remains constant for a determined length of time, after whichit drops abruptly to a lower value, where it remains constant during theremainder of the delivery. The various modes of delivery shown in thediagram can be arranged by means of the device of the invention.

FIG. 2 shows a partly sectional view of a delivery unit of the apparatusof the invention.

The delivery unit comprises a sleeve 1, which has an opening 2, throughwhich may be inserted an injection cartridge 3. At its other end, thesleeve 1 has a smaller opening 4 and an internal flange 5, against whichthe outlet end of the cartridge 3 rests. The smaller opening 4 isprovided with a threaded connecting tube 6, onto which is screwed athreaded connecting piece 7. As shown in FIG. 1, this connecting piece 7assures the connection between the smaller opening 4 of the sleeve 1 anda flexible tube 8, which at its other end is connected to a hypodermicneedle 9. An adhesive tape 10 is provided for securing the needleassembly to the skin of the patient. It is of course also possible toconnect the needle 9 directly to the connecting piece 7 without anyintervening tube.

The injection cartridge 3 may be of a conventional construction. Itcontains a liquid 11 to be injected, and is closed at its rear end by aplunger or piston 12. This plunger may have a recess 13 at its rear endfor receiving a connecting rod, as will be more closely explainedhereinafter.

At its front end, the injection cartridge 3 is closed in a conventionalway by a rubber septum which is held in place by a metal capsule 14. Theconnection between the cartridge 3 and the tube 8 via the connectingpiece 7 also comprises a hollow needle (not shown), which in a known waypierces the rubber septum such that a liquid connection is establishedbetween the interior of the cartridge and the tube 8 with the needle 9.

In the drawing, the injection cartridge 3 is shown as a simple,single-chamber cartridge. However, it may also be a dual-chambercartridge containing a dry active substance in one of the chambers and aliquid in the other, the two chambers being separated by a movable wall.Usually, the dry substance is in the front chamber and the liquid in therear one. In the wall of the cartridge is arranged a bypass channelwhich may be operative or inoperative, depending on the position of theseparating movable wall.

When the dual-chamber cartridge is to be made ready for use, the rearplunger is moved forward and will then also displace the liquid in therear chamber forward. As the liquid is largely incompressible, it willin its turn urge the movable wall forward until it is such a positionthat the rear opening of the bypass channel is exposed to the liquid.The further movement of the rear plunger will then force the liquidthrough the bypass channel into the front chamber to dissolve the drysubstance.

This arrangement is very suitable for the administering of substanceswhich are too unstable to be stored in the form of a solution, such ascertain hormones and proteins. In this way, the solution is not prepareduntil immediately before it is to be administered, and the mixingprocess can be made very carefully for delicate substances. The use of adual-chamber cartridge is a preferred embodiment of the invention.

An important feature of the apparatus is that a flow restriction isarranged in the flow path of the liquid from the injection cartridge 3to the hypodermic needle 9. This restriction may be arranged in theconnecting piece 7 and may, for example, be a constriction, such as acapillary in the flow path of the liquid. The diameter of theconstriction is adapted to the liquid to be injected such that asuitable flow is obtained. This adaption can be carried out by a personskilled in the art on the basis of simple routine tests.

The flow restriction may also be arranged in other ways. Thus, the tube8 and/or the needle 9 for administering may themselves be of suchdimensions that they act as a suitable restriction.

The flow restriction may also be adjustable, and may, for instance, bearranged as an adjustable clamp on the flexible tube 8.

The sleeve 1 is also provided with means for joining the delivery unitto the power unit shown in FIG. 2. These means may be arranged as abayonet lock 15. Other arrangements for the joining are also possible,such as a snap joint or a threaded joint for screwing the two unitstogether. It is important that the joint is secure, but yet can bereleased when desired.

FIG. 3 is a sectional view of the power unit of an apparatus of theinvention. This section comprises a sleeve 21 which is arranged to fitsnugly over the rear part of the sleeve 1 of the delivery unit shown inFIG. 1. Means 22 are provided to cooperate with the means 15 (FIG. 1) tolock the two sleeves releasably together, such as by a bayonet lock.

The sleeve 21 is closed at its rear end by an end wall 23, which isshaped as a flange. To this flange is releasably attached the flange 24of a cylinder 25. An airtight seal between the two flanges is assured bya sealing ring 26.

At its rear end, the cylinder 25 is provided with a shoulder 27, and iscontinued by a cylindrical coaxial portion 29 which has a smallerdiameter than the cylinder 25. This rear portion 29 is provided with anexternal thread 30, on to which can be screwed an internally threadedcap 31. The cap 31 is closed at its rear end by a transversal wall 32,which has an aperture 33. Through this aperture 33, the internal space34 in the cylinder 25 is in communication with the outside atmosphere.

Inside the threaded cap 31 and the cylindrical portion 29 is arranged ahelical pressure spring 35 with its front end 36 protruding into thespace 34 of the cylinder 25. The spring 35 is secured to the front faceof the transversal wall 32 of the cap 31, and the distance which thefront end 36 of the spring 35 protrudes into the space 34 can beregulated by screwing the threaded cap 31 more or less forward by meansof the thread 30 on the cylindrical portion 29.

Inside the cylinder 25 is arranged a piston 37, which is in sealingcontact with the interior wall of the cylinder via the sealing ring 38.In its resting postion, the piston rests on the rear surface of the endwall 23 of the sleeve 21.

To the front side of the piston is attached a piston rod 39, whichsealingly traverses the end wall 23 through an orifice 40. An airtightseal between the piston rod 39 and the wall of the orifice 40 is assuredby the sealing ring 41.

Thus, when the piston rod 39 and the piston 37 are moved rearward, therewill be a vacuum established in the cylinder 25 in front of the piston37, while the atmospheric pressure will prevail in the cylinder behindthe piston, as this part of the cylinder is connected to the ambientatmosphere through the orifice 33.

FIG. 4 shows the apparatus of the invention in an assembled state andready for use. The sleeve 21 of the power unit has been placed aroundthe rear part of the sleeve 1 of the delivery unit, and the two sleeveshave been locked securely together by means of the bayonet lock 15, 22.

When the two sleeves 1, 21 are coaxially brought together, the forwardend of the piston rod 39 will engage the recess 13 in the rear end faceof the plunger 12 of the injection cartridge 3, to rest securely in saidrecess. The rod 39 and the piston 37 will then be moved rearward in thecylinder 25 as the two sleeves are brought together, so that a spacewill be established in the cylinder in front of the piston 29. Becauseof the seals made by the sealing rings 26, 38 and 41, no air can enterthis space, so that a vacuum will be established therein. On the otherside of the piston 37, the atmospheric air pressure acts on the piston,as the cylinder on this side is in connection with the ambientatmosphere through the orifice 33.

When the two sleeves 1, 21 have been locked together by means of thebayonet lock 15, 22, the piston 37 will be at its most rearward positionin the cylinder 25. In the space in front of the piston in the cylinder,there will be a substantially complete vacuum, as the piston in itsinitial postion has rested on the end wall 23 of the sleeve 21, andthere is essentially no space in front of it.

When the piston 37 is moved rearward through the assembly of thedelivery unit and the power unit, its rear face will strike the frontend 36 of the helical spring 35, and further rearward movement of thepiston 37 will cause said helical spring to be compressed. The degree ofcompression of the spring may be regulated by screwing the threaded cap31 more or less far onto the thread 30 of the cylindrical portion 29.

The atmospheric pressure will now act on the rear face of the piston 37to force it forwards against the vacuum which has been established inthe major part of the space 34 in the cylinder 25. Furthermore, theforce of the compressed spring 35 will contribute to the force exertedby the atmospheric pressure. The combined force will be transmitted bythe piston rod 38 to act on the rear face of the plunger 12 in theinjection cartridge 3 to force the liquid 11 in the cartridge outthrough the tube 8 and the needle 9.

FIG. 5 shows another embodiment of the delivery unit of the apparatus ofthe invention. In this embodiment, the front part of the power unit isthe same as shown in FIGS. 3 and 4, and it is intended to be connectedto a delivery unit which is the same as that shown in FIG. 2. Thus, thepower unit comprises a front sleeve 21 with means 22 for connecting itwith the delivery unit, and a cylinder 25, in which is arrangedsealingly a piston 37 having a piston rod 39, which sealingly traversesan aperture 40 in the end wall 23.

At its rear end, the cylinder 25 is terminated by a transversal wall 50,which has an opening 51. Through this opening 51, the internal space 34of the cylinder 25 is in open connection with the ambient atmosphere.

Near its rear end, the cylinder 25 is surrounded by a second cylinder52, which is coaxial with the first cylinder 25. This second cylinder 52is connected to the first cylinder 25 by a shoulder part 53, and extendsrearwards, usually--but not necessarily--for some distance beyond therear end of the first cylinder 25. Thus, an annular space is formedbetween the outside of the first cylinder 25 and the inside of thesecond cylinder 52.

In this annular space is arranged an annular piston 54, which is sealedagainst the walls of the annular space by means of the sealing rings 55and 56. The annular piston 54 is connected to a yoke 57. In the figure,this yoke 57 is shown having two arms 58 connected to the annular piston54, but it goes without saying that the yoke may be provided with morethan two arms.

The transversal part of the yoke 57 is provided with a threaded hole 59,wherein is arranged a screw 60. The hole 59 and the screw 60 arepreferably coaxial with the first and second cylinders 25 and 52. Thefront end 61 of the screw 60 protrudes through the opening 51 into thespace 34 of the cylinder 25 for a certain distance, which may beadjusted by rotating the screw 60 by means of the knurled head 62 at itsrear end.

The annular piston 54 may be moved rearward in the annular cylinder 52by moving the yoke 57. In its initial position, the annular piston 54rests against the shoulder part 53 at the forward end of the secondcylinder 52, and there is essentially no free space in front of saidpiston 54. Thus, when the annular piston 54 is displaced rearward, therewill be established a vacuum in the space created in front of it, as itis sealed against the walls of the annular cylinder by means of thesealing rings 55 and 56. The rear face of the annular piston 54 isexposed to the ambient atmosphere, and thus the atmospheric pressurewill strive to move the annular piston 54 forward against the vacuum infront of it.

FIG. 6 shows the power unit of FIG. 5 connected to the delivery unit ofFIG. 2. It will be seen that the connection arrangement between thedelivery unit and the power unit is the same as has been describedpreviously for FIG. 4. The difference between the two arrangements isapparent at the rear end of the power unit.

When the piston 37 is moved rearward by the assembly of the deliveryunit and the power unit, its rear face will strike the front end 61 ofthe screw 60. Further rearward movement of the piston 37 will move thescrew 60 and the yoke 57 rearward. As the annular piston 54 is connectedto the yoke 57 by means of the arms 58, it will also be moved rearwardin the annular cylinder, such that a vacuum is established in the space63 of the annular cylinder. The distance that the annular piston 54 ismoved rearward in the annular cylinder can be adjusted by turning thescrew 60 by means of the knurled head 62.

The function of the apparatus of the invention is as follows:

When the apparatus is to be made ready for use, a fresh injectioncartridge 3 is inserted into the sleeve 1 of the delivery unit, which isthen connected to the power unit by means of the sleeve 21 and thelocking means 15 and 22. When the two units are brought together, thefront end of the piston rod 39 will engage the recess 13 in the rearface of the plunger 12 of the injection cartridge 3, and the piston 37will be urged rearward in the cylinder 25. A vacuum will then beestablished in the cylinder 25 in front of the piston 37, and as thespace of the cylinder behind the piston 37 is in connection with theambient atmosphere, the atmospheric pressure will strive to move thepiston 37 forward.

During the rearward travel of the piston 37 in the cylinder 25, the rearface of the piston will strike the front end 36 of the spring 35, asshown in FIG. 4, or the front end 61 of the screw 60, as shown in FIG.6. Further rearward movement of the piston 37 will be against the addedforce of the spring 35 (FIG. 4), or against the additional force of theatmospheric pressure acting against the vacuum established in theannular cylinder space 63 (FIG. 6).

When a liquid preparation is to be administered from the injectioncartridge 3, a liquid connection is opened at the front end of thecartridge by piercing its rubber septum with a hollow needle inconnection with the connecting piece 7 and the tube 8. This liquidconnection may also be established before the delivery unit and thepower unit are joined to each other. The restriction in the flow path ofthe liquid is preferably closed at this stage.

When the restriction is opened to a suitable degree, the force acting onthe piston 37 will be transmitted by the piston rod 39 to the plunger 12of the injection cartridge 3, to urge said plunger forward and expel theliquid preparation from said cartridge. In the initial stage of themovement forward of the piston 37, an auxiliary force will act on it inaddition to the force exerted by the atmospheric pressure on said piston37. This auxiliary force will act in accordance with one of twoembodiments of the invention:

In the first embodiment, shown in FIG. 4, the auxiliary force is exertedby a compressed spring. As the force exerted by a spring is proportionalto its compression, this means that the auxiliary force is greatest whenthe spring is most compressed, and will decrease in an approximatelylinear manner as the compression decreases. Futhermore, the amountexpelled from the injection cartridge per unit of time is approximatelyproportional to the force acting on the plunger 12. This means that inthe initial stage of the administration, the amount administered willdecrease in a substantially linear way with time.

When the piston 37 has traveled so far forward that its rear face is nolonger in contact with the spring 35, the auxiliary force from saidspring will end. During the further forward travel of the piston 37, itwill only be driven forward by the atmospheric pressure acting againstthe vacuum in the cylinder 25 in front of said piston. This force isconstant as long as there exists a vacuum, which means that theadministered amount will also be constant with time.

The combined result of the two forces acting on the piston 37 inaccordance with the first embodiment will then be an administering modewhich is illustrated by graph B in FIG. 1. It will be seen that theadministered amount is high at the beginning and then decreases in alinear manner uptil it reaches a constant value, which is maintaineduntil the end of the administering.

In the second embodiment, shown in FIG. 6, the auxiliary force isexerted by the atmospheric pressure acting on the annular piston 54 inthe annular cylinder between the first cylinder 25 and the secondcylinder 52. This auxiliary force will remain constant as long as thereexists a vacuum in front of the annular piston 54.

When the piston 37 has traveled so for forward that its rear face is nolonger in contact with the front end 61 of the screw 60, the annularpiston 54 will rest against the rear face of the shoulder part 53 of thesecond cylinder 52, and there will no longer exist any vacuum in frontof said annular piston. This means that the auxiliary force will cease,and during the further forward travel of the piston 37, it will only bedriven by the atmospheric pressure acting on its rear face. This forceis also constant as long as there exists a vacuum in front of the piston37.

The combined result of the two forces acting on the piston 37 inaccordance with the second embodiment will be an administering modewhich is illustrated by graph C in FIG. 1. It will be seen that as longas the atmospheric pressure acts on the annular piston 54 as well as onthe piston 37, the administered amount remians at a constant high value.When the auxiliary force from the annular piston ceases, theadministered amount decreases abruptly to a new value, which remainsconstant until the end of the administering

In the apparatus according to the first embodiment of the invention,which is illustrated in FIGS. 3 and 4, the mode of administering may beadjusted by means of the threaded cap 31. The spring 35 is attached tothe front face of the rear transversal wall 32 of the cap 31, and byscrewing this cap onto the external thread 30 for a shorter or longerdistance, it is possible to adjust the distance by which the front end36 of the spring 35 protrudes into the cylinder 25. This distancedetermines for how much of the travel of the piston 37 that the spring35 will exert its auxiliary force. The magnitude of this auxiliary forcemay be adjusted by selecting a spring 35 having a suitable stiffness.Thus, if the spring 35 protrudes into the cylinder 25 for a longdistance, the initial auxiliary force will be higher, and it will take alonger time for it to decrease to zero, when the constant force on thepiston 37 will prevail.

In the apparatus according to the second embodiment of the invention,which is illustrated in FIGS. 5 and 6, the mode of administrering may beadjusted by means of the screw 60, which is threaded through the crosspart of the yoke 57. If the screw 60 is screwed through the yoke 57 farinto the cylinder 25, the rear face of the piston 37 will strike thefront end 61 of the screw 60 earlier on its travel rearward. This meansthat the annular piston 54 will be moved rearward a greater distanceagainst the vacuum established in front of it. On the following forwardmovement of the piston 37, the auxiliary force exerted by the annularpiston through the yoke 57 will therefore act for a longer time. Ingraph C in FIG. 1, the administering will then be made at the higherconstant value for a longer time before it drops to the lower constantvalue. The magnitude of the auxiliary force in this embodiment isdetermined by the area of the annular piston 54 which is subjected tothe atmospheric pressure.

It is to be noted that in the second embodiment of the invention, thesecond piston and cylinder assembly does not necessarily have to bearranged as an annular piston in an annular cylinder which encircles thefirst cylinder, as shown in FIGS. 5 and 6. Instead, the second cylindermay consist of an arrangement of a number of cylinders arranged alongthe exterior wall of the first cylinder, preferrably equidistantly, andhaving their axes essentially parallel with that of the first cylinder.In each of these second cylinders is then arranged a piston, and allthese pistons are connected with a yoke, as shown in FIGS. 5 and 6. Thisarrangement will function in the same way as has been described in theforegoing, but its construction is somewhat more complicated.

In all other respects than the arrangement of the auxiliary force, theapparatus of the invention is arranged as is known from the prior art.Thus, the delivery unit is as described in the international patentapplication PCT/SE91/00506, and can comprise a single-chamber or adual-chamber injection cartridge. The dual-chamber cartridge embodimentis preferred. In this case the preparation of the dual-chamber cartridgefor injection in a manner known per se takes place in the initial stageof the assembling together of the delivery unit and the power unit. Therear piston of the cartridge will then be moved forward in the rearchamber of the cartridge to urge the front piston forward to expose thebypass channel and conduct the liquid from said rear chamber into thefront chamber, to be mixed with the solid components therein. The designmodifications which will be necessary are clearly apparent to personsskilled in the art.

It is an important feature of the apparatus of the invention that thedelivery unit and the power unit are arranged along a common axis. Inthis way, the power unit will be actuated immediately when the two unitsare joined together, and the force of the piston will be transmitted ina linear direction from the power unit directly to the plunger in thedelivery unit by means of the direct mechanical connection in the formof the piston rod.

The outflow of the liquid preparation from the delivery unit iscontrolled by a restriction in the flow path of the liquid, as describedpreviously. This restriction may be constant and in the form of acapillary arranged in the flow path, or it may be variable and bearranged as a clamp on the outflow tube, for example. The flow path maybe closed initially, and may then be gradually opened up when theadministering starts.

The restriction is usually set such that the liquid in the cartridgewill be administered for a time of at least about 30 minutes, andusually for an hour or more. However, these times are not critical tothe invention, and may be set within very wide limits, from about asecond up to 24 hours or more.

When the contents of the cartridge has been administered, the bayonetlock 15,22 is released and the two units are taken apart from eachother. Under the influence of the atmospheric pressure, the piston 37 inthe cylinder 25 of the power unit will then return to its foremostposition. From the delivery unit, the injection cartridge 3 is removedthrough the rear opening 2, and is discarded. The connecting piece 7 isunscrewed from the connecting tube 6, so that the tube 8 with thehypodermic needle 9 at one of its ends and the connecting needle at itsother end may be removed and discarded. A fresh cartridge may then beinserted into the sleeve 1 of the delivery unit, which may then again beconnected with the power unit for a new administering. The liquidconnection with the interior of the cartridge may be established beforeor after the delivery unit and the power unit have been connectedtogether.

An advantage of the apparatus of the invention is tha the sleeve of thedelivery unit and the complete power unit may be re-used an infinitenumber of times, and they do not have to be extensively sterilized, asthey will not get into contact with the liquid preparation to beadministered. The power unit with its auxiliary power units is notdependent on any external energy source, and the vacuum whichconstitutes its driving force is not established until immediatelybefore the apparatus is to be used. This greatly diminishes the risks ofpossible leaks. Also, the driving and auxiliary forces are largelyindependent of variations in temperature. Both the delivery unit and thepower unit are simple in their construction, and are thereforeinexpensive to manufacture.

The choice of materials for the apparatus is not critical, and suitablematerials may easily be selected by those skilled in the art. It isoften desirable that the apparatus may be easily sterilized, forinstance by autoclaving at en elevated temperature of at least about120° C. Various plastic materials are suitable, and also metals, such asstainless steel and aluminum alloys.

In the foregoing, it has been pointed out that the use of an injectioncartridge, especially of the dual-chamber type, is a preferredembodiment of the invention. However, this is not the only possibleembodiment. It is also possible to use the sleeve 1 itself of thedelivery unit as a container or syringe for the liquid preparation. Forfilling this container, the liquid is drawn up from a suitable liquidreservoir through a needle attached to the front end of the sleeve, bymeans of a suitably arranged plunger in the sleeve. After the containerhas been filled in this way, the further function of the apparatus is asdescribed in the foregoing.

It is to be noted that the present invention is not limited to only theembodiments specifically shown in the drawings and described in theforegoing specification. To a person skilled in the art, other variantsand modifications are possible without departing from the scope of theinvention as defined by the appended claims.

I claim:
 1. Apparatus for a controlled time-variable delivery of aliquid preparation from a cylindrical liquid container having at itsfront end a liquid outlet provided with a constriction, and at its rearend a movable wall, which functions like a piston to expel said liquidfrom said container through said outlet, said rear movable wall beingurged forward by mechanical action by a force which is generated by theatmospheric pressure urging a first piston into a first essentiallyempty vacuum space, and characterized in that auxiliary means arearranged to act on said movable wall by exerting a supplementary forceon said first piston at the initial stage of its movement into saidfirst vacuum space.
 2. Apparatus according to claim 1, characterized inthat said auxiliary means is a pressure spring which acts on said firstpiston against said vacuum space.
 3. Apparatus according to claim 1,characterized in that said auxiliary means comprise at least oneauxiliary space wherein essentially a vacuum has been established andwherein the atmospheric pressure acts on at least one auxiliary piston,which is mechanically coupled to said first piston in said first vacuumspace.
 4. Apparatus according to claim 1, characterized in that itcomprises a delivery unit, which contains the container for the liquidpreparation, and a power unit, which comprises a first cylinder whichcontains said first vacuum space and said first piston, the two unitsbeing assembled coaxially such that at the assembling, said first pistonhas been urged rearward in said first cylinder by means of a piston rodsuch that said first vacuum space has been established in front of saidfirst piston and the atmospheric pressure exerts a forward driving forceon said first piston, this driving force acting on the movable wall ofsaid container for the liquid preparation by means of said piston rodand striving to urge said movable wall forward, and that said auxiliarymeans are arranged near the rear end of said first cylinder to cooperatewith the atmospheric pressure at the initial stage of the forwardmovement of said first piston.
 5. Apparatus according to claim 4,characterized in that a pressure spring is arranged within said firstcylinder on the rear side of said first piston in such a way that itexerts a forward directed pressure force on said first piston at theinitial stage of its forward movement.
 6. Apparatus according to claim4, characterized in that near the rear end of the first cylinder isarranged at least one second cylinder wherein a second piston isarranged movable and mechanically coupled to said first piston in such away that when said first piston is moved rearward, said second piston isalso moved rearward, establishing a space with essentially a vacuum insaid second cylinder.
 7. Apparatus according to claim 6, characterizedin that said second cylinder is arranged in annular arrangement aroundsaid first cylinder near its rear end, said second piston being annularand arranged movably in said second cylinder.
 8. Apparatus according toclaim 1, characterized in that a mechanism is arranged to adjust thedistance which said first piston is acted on by said auxiliary meansduring its travel forward.
 9. Apparatus according to claim 8,characterized in that said mechanism is a screw mechanism.
 10. Apparatusaccording to claim 1, characterized in that said container for theliquid preparation is an injection cartridge having one or morechambers.
 11. Apparatus according to claim 2, characterized in that itcomprises a delivery unit, which contains the container for the liquidpreparation, and a power unit, which comprises a first cylinder whichcontains said first vacuum space and said first piston, the two unitsbeing assembled coaxially such that at the assembling, said first pistonhas been urged rearward in said first cylinder by means of a piston rodsuch that said first vacuum space has been established in front of saidfirst piston and the atmospheric pressure exerts a forward driving forceon said first piston, this driving force acting on the movable wall ofsaid container for the liquid preparation by means of said piston rodand striving to urge said movable wall forward, and that said auxiliarymeans are arranged near the rear end of said first cylinder to cooperatewith the atmospheric pressure at the initial stage of the forwardmovement of said first piston.
 12. Apparatus according to claim 3,characterized in that it comprises a delivery unit, which contains thecontainer for the liquid preparation, and a power unit, which comprisesa first cylinder which contains said first vacuum space and said firstpiston, the two units being assembled coaxially such that at theassembling, said first piston has been urged rearward in said firstcylinder by means of a piston rod such that said first vacuum space hasbeen established in front of said first piston and the atmosphericpressure exerts a forward driving force on said first piston, thisdriving force acting on the movable wall of said container for theliquid preparation by means of said piston rod and striving to urge saidmovable wall forward, and that said auxiliary means are arranged nearthe rear end of said first cylinder to cooperate with the atmosphericpressure at the initial stage of the forward movement of said firstpiston.
 13. Apparatus according to claim 2, characterized in that amechanism is arranged to adjust the distance which said first piston isacted on by said auxiliary means during its travel forward. 14.Apparatus according to claim 3, characterized in that a mechanism isarranged to adjust the distance which said first piston is acted on bysaid auxiliary means during its travel forward.
 15. Apparatus accordingto claim 4, characterized in that a mechanism is arranged to adjust thedistance which said first piston is acted on by said auxiliary meansduring its travel forward.
 16. Apparatus according to claim 5,characterized in that a mechanism is arranged to adjust the distancewhich said first piston is acted on by said auxiliary means during itstravel forward.
 17. Apparatus according to claim 6, characterized inthat a mechanism is arranged to adjust the distance which said firstpiston is acted on by said auxiliary means during its travel forward.18. Apparatus according to claim 7, characterized in that a mechanism isarranged to adjust the distance which said first piston is acted on bysaid auxiliary means during its travel forward.
 19. Apparatus accordingto claim 2, characterized in that said container for the liquidpreparation is an injection cartridge having one or more chambers. 20.Apparatus according to claim 3, characterized in that said container forthe liquid preparation is an injection cartridge having one or morechambers.